Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.4.2.30 (PARP)
 13,611 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In extraskeletal myxoid chondrosarcoma, a chromosomal translocation creates a gene fusion between EWS and an orphan nuclear receptor, NOR1. The resulting fusion protein EWS/NOR1 has been believed to lead to malignant transformation by functioning as a transactivator for NOR1-target genes. By comparing the gene expression profiles of NOR1- and EWS/NOR1-overexpressing cells, we found that they largely shared up-regulated genes, but no significant correlation was observed with respect to the transactivation levels of each gene. In addition, the proteins associated with NOR1 and EWS/NOR1 were mostly the same in these cells. The results suggest that these proteins differentially transactivate overlapping target genes through a similar transcriptional machinery. To clarify the mechanisms underlying the transcriptional divergence between NOR1 and EWS/NOR1, we searched for alternatively associated proteins, and identified poly(ADP-ribose) polymerase I (PARP-1) as an NOR1-specific binding protein. Consistent with its binding properties, PARP-1 acted as a transcriptional repressor of NOR1, but not EWS/NOR1, in a luciferase reporter assay employing PARP-1(-/-) fibroblasts. Interestingly, suppressive activity of PARP-1 was observed in a DNA response element-specific manner, and in a subtype-specific manner toward the NR4A family (Nur77, Nurr1, and NOR1), suggesting that PARP-1 plays a role in the diversity of transcriptional regulation mediated by the NR4A family in normal cells. Altogether, our findings suggest that NOR1 and EWS/NOR1 regulate overlapping target genes differently by utilizing associated proteins, including PARP-1; and that EWS/NOR1 may acquire oncogenic activities by avoiding (or gaining) transcription factor-specific modulation by the associated proteins.
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PMID:Differential transactivation by orphan nuclear receptor NOR1 and its fusion gene product EWS/NOR1: possible involvement of poly(ADP-ribose) polymerase I, PARP-1. 1868 Jan 43

Autophagy is a cellular survival mechanism that involves the catabolic degradation of damaged proteins and organelles during stress. It is particularly required for tumor cell survival during starvation and tumorigenesis. NOR1 is a putative tumor suppressor gene. This study investigated in vitro the effects of NOR1 on the regulation of nasopharyngeal carcinoma autophagy, metabolism, and apoptosis. The data showed that acute oxidative stress induced the expression of NOR1 in normal human cells and tumor cells. Restoration of NOR1 expression downregulated basal autophagy, assessed by autophagy marker LC3 conversion and transmission electron microscopy. In NOR1-expressing tumor cells, reduced autophagy inhibited mitochondrial respiration and energy metabolism. Restoration of NOR1 expression in nasopharyngeal carcinoma cells enhanced apoptosis after induction of oxidative stress. NOR1 expression upregulated Bax expression, Bax translocation to the mitochondria, Smac/DIABLO release from the mitochondria, and activation of caspase-9, and -3, and PARP. In contrast, knockdown of NOR1 expression using NOR1 RNAi resulted in an increase in autophagy and attenuated hydrogen peroxide-induced cell death in HeLa cells. In addition, expression of NOR1 significantly inhibited cisplatin-induced autophagy, resulting in increased cisplatin cytotoxicity and apoptosis. These data revealed novel aspects of the interplay between autophagy and apoptosis in nasopharyngeal carcinoma cells, which underlies the tumor suppression function of NOR1. This work may provide novel insights to contribute to the development of a combinatorial therapy for nasopharyngeal carcinoma.
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PMID:Tumor suppressor gene Oxidored-nitro domain-containing protein 1 regulates nasopharyngeal cancer cell autophagy, metabolism, and apoptosis in vitro. 2383 7